General MedicationsORALHigh Alert

CREXONT

CARBIDOPA AND LEVODOPA

Standard Dose

2 DOSAGE AND ADMINISTRATION Evaluate vitamin B6 levels prior to starting treatment with carbidopa/levodopa therapies. ( 2.1 ) Levodopa-naïve patients: Starting dose is 35 mg carbidopa / 140 mg levodopa taken orally twice daily for the first 3 days; on the fourth day of treatment, dosage may be increased gradually as needed. ( 2.2 ) Patients converting from immediate-release carbidopa/levodopa: See Table 1 for instructions; dosages are not substitutable on a 1:1 basis. ( 2.3 ) The maximum recommended daily dosage of CREXONT is 525 mg carbidopa / 2100 mg levodopa. ( 2.2 , 2.3 ) CREXONT may be taken with or without food; do not chew, divide, or crush. ( 2.5 , 12.3 ) CREXONT should not be taken with alcohol. ( 2.5 , 12.3 ) 2.1 Management of Vitamin B6 Levels Evaluate vitamin B6 levels prior to initiating carbidopa/levodopa therapies, including CREXONT, periodically during treatment, and as clinically indicated [see Warnings and Precautions (5.7) ]. If vitamin B6 levels are low, supplement to sufficient levels per standard of care. Patients may initiate and continue treatment with CREXONT while supplementing vitamin B6. 2.2 Dosage in Patients Naïve to Levodopa Therapy The recommended starting dosage of CREXONT in levodopa-naïve patients is 35 mg carbidopa / 140 mg levodopa taken orally twice daily for the first three days. Thereafter, dosage may be increased gradually as needed to a maximum daily dosage of 525 mg carbidopa / 2100 mg levodopa divided up to four times daily. 2.3 Dosage in Patients Converting from Immediate-Release Carbidopa-Levodopa to CREXONT The dosages of immediate-release carbidopa-levodopa products are not substitutable on a 1:1 basis with the dosages of CREXONT. To convert patients from immediate-release carbidopa-levodopa to CREXONT, follow these steps: Step 1: Determine the patient’s total daily dosage of immediate-release levodopa. Step 2: Determine the patient’s most frequent single dose of immediate-release levodopa. If more than one dose corresponds to the most frequent, use the highest of the doses. Step 3: Find the values from Step 1 and Step 2 in Table 1 (below) to determine the recommended starting CREXONT dosage of levodopa and dosing frequency. Step 4: After one to three days, adjust the dose or frequency as needed based on the patient’s clinical response and tolerability. Dosage may be increased gradually as needed to a maximum daily dosage of 525 mg carbidopa / 2100 mg levodopa divided up to four times daily. Table 1: Conversion from Immediate-Release Carbidopa-Levodopa to CREXONT Total Daily Immediate-Release Levodopa Dosage Most Frequent Immediate-Release Levodopa Single Dose Recommended Starting CREXONT Dosage of Levodopa Less than 500 mg daily 100 mg 280 mg twice daily 150 mg 420 mg twice daily 200 mg 560 mg twice daily Equal to or greater than 500 mg daily 100 mg 280 mg three times daily 150 mg 420 mg three times daily 200 mg 560 mg three times daily Greater than 200 mg 700 mg three times daily For patients currently treated with carbidopa and levodopa plus a catechol-O-methyl transferase (COMT) inhibitor (e.g., entacapone or opicapone), the initial total daily dose of levodopa in CREXONT may need to be increased if the COMT inhibitor is discontinued. Use of CREXONT in combination with other levodopa products has not been studied. 2.4 Dosage for Patients Converting from Extended-Release Carbidopa-Levodopa (Rytary) to CREXONT For patients converting from RYTARY (extended-release carbidopa-levodopa), initiate CREXONT on an approximately 1:1 mg basis using the levodopa component for conversion. 2.5 Administration Information Swallow CREXONT whole with or without food. CREXONT should not be taken with alcohol. A high-fat, high-calorie meal may delay the absorption of levodopa to reach the peak plasma concentration by about 2 hours [see Clinical Pharmacology (12.3) ]. Do not chew, divide, or crush CREXONT capsules. 2.6 Discontinuation of CREXONT Avoid sudden discontinuation or rapid dose reduction of CREXONT. The daily dose of CREXONT should be tapered at the time of treatment discontinuation [see Warnings and Precautions (5.2) ] .

Max Dose

See official label

Primary Use

1 INDICATIONS AND USAGE CREXONT is indicated for the treatment of Parkinson's disease, post-encephalitic parkinsonism, and parkinsonism that may follow carbon monoxide intoxication or manganese intoxication in adults.

Summary

CREXONT is a combination of carbidopa (an aromatic amino acid decarboxylation inhibitor) and levodopa (an aromatic amino acid) indicated for the treatment of Parkinson’s disease, post-encephalitic parkinsonism, and parkinsonism that may follow carbon monoxide intoxication or manganese intoxication in adults. ( 1 ) Dosage and administration 2 DOSAGE AND ADMINISTRATION Evaluate vitamin B6 levels prior to starting treatment with carbidopa/levodopa therapies. ( 2.1 ) Levodopa-naïve patients: Starting dose is 35 mg carbidopa / 140 mg levodopa taken orally twice daily for the first 3 days; on the fourth day of treatment, dosage may be increased gradually as needed. ( 2.2 ) Patients converting from immediate-release carbidopa/levodopa: See Table 1 for instructions; dosages are not substitutable on a 1:1 basis. ( 2.3 ) The maximum recommended daily dosage of CREXONT is 525 mg carbidopa / 2100 mg levodopa. ( 2.2 , 2.3 ) CREXONT may be taken with or without food; do not chew, divide, or crush. ( 2.5 , 12.3 ) CREXONT should not be taken with alcohol. ( 2.5 , 12.3 ) 2.1 Management of Vitamin B6 Levels Evaluate vitamin B6 levels prior to initiating carbidopa/levodopa therapies, including CREXONT, periodically during treatment, and as clinically indicated [see Warnings and Precautions (5.7) ].

Structured Monograph

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE CREXONT is indicated for the treatment of Parkinson's disease, post-encephalitic parkinsonism, and parkinsonism that may follow carbon monoxide intoxication or manganese intoxication in adults. CREXONT is a combination of carbidopa (an aromatic amino acid decarboxylation inhibitor) and levodopa (an aromatic amino acid) indicated for the treatment of Parkinson’s disease, post-encephalitic parkinsonism, and parkinsonism that may follow carbon monoxide intoxication or manganese intoxication in adults. ( 1 ) Dosage and administration 2 DOSAGE AND ADMINISTRATION Evaluate vitamin B6 levels prior to starting treatment with carbidopa/levodopa therapies. ( 2.1 ) Levodopa-naïve patients: Starting dose is 35 mg carbidopa / 140 mg levodopa taken orally twice daily for the first 3 days; on the fourth day of treatment, dosage may be increased gradually as needed. ( 2.2 ) Patients converting from immediate-release carbidopa/levodopa: See Table 1 for instructions; dosages are not substitutable on a 1:1 basis. ( 2.3 ) The maximum recommended daily dosage of CREXONT is 525 mg carbidopa / 2100 mg levodopa. ( 2.2 , 2.3 ) CREXONT may be taken with or without food; do not chew, divide, or crush. ( 2.5 , 12.3 ) CREXONT should not be taken with alcohol. ( 2.5 , 12.3 ) 2.1 Management of Vitamin B6 Levels Evaluate vitamin B6 levels prior to initiating carbidopa/levodopa therapies, including CREXONT, periodically during treatment, and as clinically indicated [see Warnings and Precautions (5.7) ]. If vitamin B6 levels are low, supplement to sufficient levels per standard of care. Patients may initiate and continue treatment with CREXONT while supplementing vitamin B6. 2.2 Dosage in Patients Naïve to Levodopa Therapy The recommended starting dosage of CREXONT in levodopa-naïve patients is 35 mg carbidopa / 140 mg levodopa taken orally twice daily for the first three days. Thereafter, dosage may be increased gradually as needed to a maximum daily dosage of 525 mg carbidopa / 2100 mg levodopa divided up to four times daily. 2.3 Dosage in Patients Converting from Immediate-Release Carbidopa-Levodopa to CREXONT The dosages of immediate-release carbidopa-levodopa products are not substitutable on a 1:1 basis with the dosages of CREXONT. To convert patients from immediate-release carbidopa-levodopa to CREXONT, follow these steps: Step 1: Determine the patient’s total daily dosage of immediate-release levodopa. Step 2: Determine the patient’s most frequent single dose of immediate-release levodopa. If more than one dose corresponds to the most frequent, use the highest of the doses. Step 3: Find the values from Step 1 and Step 2 in Table 1 (below) to determine the recommended starting CREXONT dosage of levodopa and dosing frequency. Step 4: After one to three days, adjust the dose or frequency as needed based on the patient’s clinical response and tolerability. Dosage may be increased gradually as needed to a maximum daily dosage of 525 mg carbidopa / 2100 mg levodopa divided up to four times daily. Table 1: Conversion from Immediate-Release Carbidopa-Levodopa to CREXONT Total Daily Immediate-Release Levodopa Dosage Most Frequent Immediate-Release Levodopa Single Dose Recommended Starting CREXONT Dosage of Levodopa Less than 500 mg daily 100 mg 280 mg twice daily 150 mg 420 mg twice daily 200 mg 560 mg twice daily Equal to or greater than 500 mg daily 100 mg 280 mg three times daily 150 mg 420 mg three times daily 200 mg 560 mg three times daily Greater than 200 mg 700 mg three times daily For patients currently treated with carbidopa and levodopa plus a catechol-O-methyl transferase (COMT) inhibitor (e.g., entacapone or opicapone), the initial total daily dose of levodopa in CREXONT may need to be increased if the COMT inhibitor is discontinued. Use of CREXONT in combination with other levodopa products has not been studied. 2.4 Dosage for Patients Converting from Extended-Release Carbidopa-Levodopa (Rytary) to CREXONT For patients converting from RYTARY (extended-release carbidopa-levodopa), initiate CREXONT on an approximately 1:1 mg basis using the levodopa component for conversion. 2.5 Administration Information Swallow CREXONT whole with or without food. CREXONT should not be taken with alcohol. A high-fat, high-calorie meal may delay the absorption of levodopa to reach the peak plasma concentration by about 2 hours [see Clinical Pharmacology (12.3) ]. Do not chew, divide, or crush CREXONT capsules. 2.6 Discontinuation of CREXONT Avoid sudden discontinuation or rapid dose reduction of CREXONT. The daily dose of CREXONT should be tapered at the time of treatment discontinuation [see Warnings and Precautions (5.2) ] . Warnings and cautions 5 WARNINGS AND PRECAUTIONS May cause falling asleep during activities of daily living. ( 5.1 ) Avoid sudden discontinuation or rapid dose reduction to reduce the risk of withdrawal-emergent hyperpyrexia and confusion. ( 5.2 ) Cardiovascular Events: Monitor

Monitoring

• 5 WARNINGS AND PRECAUTIONS May cause falling asleep during activities of daily living.
• ( 5.1 ) Avoid sudden discontinuation or rapid dose reduction to reduce the risk of withdrawal-emergent hyperpyrexia and confusion.
• ( 5.2 ) Cardiovascular Events: Monitor patients with a history of cardiovascular disease.
• ( 5.3 ) Hallucinations/Psychosis may occur.

Interaction Notes

• 7 DRUG INTERACTIONS Iron salts and dopamine D2 antagonists, including metoclopramide, may reduce the effectiveness of CREXONT.
• ( 7.2 , 7.3 ) 7.1 Monoamine Oxidase (MAO) Inhibitors Nonselective MAO Inhibitors The use of nonselective MAO inhibitors (e.g., phenelzine and tranylcypromine) with CREXONT is contraindicated [see Contraindications (4) ] .
• Discontinue use of any nonselective MAO inhibitors at least two weeks prior to initiating CREXONT.
• Selective MAO Inhibitors The use of selective MAO-B inhibitors (e.g., rasagiline and selegiline) with CREXONT may be associated with orthostatic hypotension.